Objective: To analyze the epidemiological characteristics and trends of other infectious diarrhea among children under 18 years old in Guangzhou City from 2014 to 2020, and to explore the correlation between climatic factors and the incidence of the disease, so as to provide reference for the early prevention of infectious diseases. Methods: The data of cases of other infectious diarrhea and meteorological data of children under 18 years old in Guangzhou City from 2014 to 2020 were collected through the Chinese Infectious Disease Reporting System and the Guangzhou Meteorological Bureau. The correlation between meteorological factors and the incidence of other infectious diarrhea was analyzed using negative binomial regression. Results: A total of 104 566 cases of other infectious diarrhea among children under 18 years old were reported in Guangzhou City from 2014 to 2020, with a male to female ratio of 1.48∶1. The incidence rate was the highest in 2017 (980.83 per 100 000) and the lowest in 2020 (388.22 per 100 000). The peak of incidence occurred from October to March of the following year. Children under 5 years old accounted for 87.95% of all cases. The number of cases of other infectious diarrhea was negatively correlated with the temperature of the previous 6 days ( IRR = -0.07 ), and positively correlated with the temperature difference on the day of onset ( IRR =0.02) (both P <0.05). It was also positively correlated with the wind speed of the previous 7 days ( IRR=0.07, P <0.05), but there was no statistically significant correlation with the relative humidity on the day of onset ( IRR=-0.00, P >0.05). Conclusions Low temperature, large temperature difference, and high wind speed can increase the risk of other infectious diarrhea. It is necessary to strengthen the prediction and early warning in conjunction with meteorological changes, and warn kindergartens and schools to enhance preventive measures against the clustering of other infectious diarrhea cases.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective:To investigate the predictive value of maximum tumor diameter and the peripheral blood neutrophil to lymphocyte ratio (NLR) before radiotherapy for the occurrence of esophageal fistula after radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) .Methods:A total of 98 patients with ESCC who underwent radiotherapy in Hefei Cancer Hospital, Chinese Academy of Sciences from February 2017 to February 2021 were selected, and the patients were divided into esophageal fistula group (13 cases) and no esophageal fistula group (85 cases) according to whether esophageal fistula occurred during the follow-up process. The prognostic nutritional index (PNI) , NLR, and systemic inflammatory response index (SIRI) were calculated. Univariate and multivariate logistic regression were used to analyze the influencing factors of esophageal fistula, and the predictive value of each indicator was evaluated by using the receiver operator characteristic (ROC) curve.Results:There were no statistically significant differences in age, smoking history, diabetes mellitus history, gender, concurrent chemotherapy and alcohol history between the esophageal fistula group and the no esophageal fistula group (all P>0.05) , while there were statistically significant differences in PNI ( t=2.24, P=0.041) , NLR ( t=3.75, P=0.001) , SIRI ( t=2.68, P=0.015) . Univariate analysis showed that tumor length ( OR=1.16, 95% CI: 1.01-1.35, P=0.043) , maximum tumor diameter ( OR=1.63, 95% CI: 1.11-2.39, P=0.012) , PNI ( OR=0.83, 95% CI: 0.71-0.98, P=0.023) , NLR ( OR=1.94, 95% CI: 1.20-3.12, P=0.007) and SIRI ( OR=1.82, 95% CI: 1.03-3.24, P=0.041) were related to esophageal fistula. Multivariate analysis showed that maximum tumor diameter ( OR=2.17, 95% CI: 1.02-4.94, P=0.033) and NLR ( OR=2.40, 95% CI: 1.89-6.59, P=0.018) were independent influencing factors for the development of esophageal fistula in patients with ESCC after radiotherapy. ROC curve analysis showed that the area under the curve of maximum tumor diameter before radiotherapy combined with NLR for predicting esophageal fistula in patients with esophageal squamous cell carcinoma after radiotherapy was 0.83 (95% CI: 0.74-0.90) , which was greater than that of maximum tumor diameter before radiotherapy (0.71, 95% CI: 0.63-0.81, Z=1.80, P=0.039) and NLR (0.74, 95% CI: 0.67-0.85, Z=1.64, P=0.046) alone. Conclusions:The maximum tumor diameter before radiotherapy and NLR are closely related to the occurrence of esophageal fistula in ESCC after radiotherapy, and these factors are expected to serve as key predictors of the occurrence of esophageal fistula.

Objective:To observe the effects of Qizhi Tongluo Prescription on renal interstitial fibrosis in rats with membranous nephropathy based on the Shh/Gli1 signaling pathway; To explore its intervention mechanism.Methods:Totally 60 male SD rats were divided into blank group ( n=10) and model group ( n=50) using random number table method. The model of membranous nephropathy was established according to the modified Border method. The successfully modeling rats were divided into model group, benazepril group and Qizhi Tongluo Prescription low-, medium- and high-dosage groups using random number table method. Benazepril group was gavaged with benazepril hydrochloride 10 mg/kg, Qizhi Tongluo Prescription low-, medium- and high-dosage groups were gavaged with Qizhi Tongluo Prescription solution 1.22 g/kg, 2.43 g/kg and 4.86 g/kg, and blank group and model group were gavaged with equal volume of normal saline, once a day, for 4 weeks. The 24-hour urine was collected to detect the 24-hour urinary protein quantification, and the blood was taken from the abdominal aorta to detect the levels of total cholesterol (TC), triglyceride(TG), and serum albumin(ALB); the pathological changes of rat kidney were observed by light microscope and transmission electron microscope; the protein expressions of sonic hedgehog factor (Shh), zinc finger protein 1 (Gli1) and α-smooth muscle actin (SMA) in renal tissues were detected by immunohistochemistry; the protein expressions of Shh, Gli1, α-SMA, TGF-β1, Collagen Ⅳ and plasminogen activator inhibitor-1 (PAl-1) in renal tissues were detected by Western blot. Results:Compared with the model group, the quantitative level of 24-hour urinary protein of rats in each administration group decreased ( P<0.05), serum TC and TG levels increased ( P<0.05), ALB level decreased ( P<0.05), the positive expressions of Shh, Gli1, α-SMA protein in renal tissue decreased ( P<0.05), and the protein expressions of Shh, Gli1, α-SMA, Collagen Ⅳ, TGF-β1, PAI-1 in renal tissue decreased ( P<0.05). Conclusion:Qizhi Tongluo Prescription can improve renal interstitial fibrosis in membranous nephropathy rats, possibly by inhibiting the Shh/Gli1 signaling pathway to delay renal interstitial fibrosis.

Lung function serves as a clinical indicator reflecting respiratory system function,ai-ding in the diagnosis and monitoring of pulmonary diseases.Both genetic and environmental factors ex-ert significant influences on lung function.A comprehensive understanding of the role of genetic factors in lung function is crucial for gaining deeper insights into the regulatory mechanisms of lung function.In recent years,with the application of advanced technologies such as genome-wide association stud-ies,whole-exome sequencing,whole-genome sequencing,and epigenome-wide association studies,numerous genetic loci related to lung function have been identified.This review aimed to summarize the current research progress in genetics related to lung function,providing a reference for subsequent in-depth exploration of the pathological and physiological mechanisms affecting lung function.

Objective:To explore the efficacy of secondary targeted percutaneous vertebroplasty (PVP) for the treatment of refracture of injured vertebrae after vertebral augmentation for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective case series study was performed on the clinical data of 25 patients with refracture of injured vertebrae after vertebral augmentation for OVCF admitted to Honghui Hospital, Xi′an Jiaotong University from January 2019 to January 2022, including 10 males and 15 females, aged 62-86 years [(73.8±5.2)years]. The fractured segments involved T 10 in 1 patient, T 11 in 2, T 12 in 10, L 1 in 10 and L 2 in 2. All the patients were treated with secondary targeted PVP. The operation time and the amount of bone cement injected were recorded. The visual analogue scale (VAS) of lower back, Oswestry disability index (ODI), vertebral body index (VBI) and kyphotic angle (KA) were compared before surgery, at 1 day, 6 months after surgery and at the last follow-up. Odom criteria were used to evaluate the efficacy of the surgical procedure at the last follow-up. The intraoperative bone cement leakage and new vertebrae fracture during follow-up were observed. Results:All the patients were followed up for 23-59 months [(36.8±7.6)months]. The operation time was 35-60 minutes [(42.6±5.2)minutes], with the amount of bone cement injected for 3-5 ml [(3.6±0.8)ml]. The VAS scores of lower back at 1 day, 6 months after surgery and at the last follow-up were 3.1(2.0, 4.0)points, 1.7(1.0, 2.0)points and 0.6(0.0, 1.0)points respectively, significantly lower than 7.6(7.0, 9.0)points before surgery ( P<0.01), and a statistically singnificant decrease was found over follow-up time ( P<0.01). The ODI values at 1 day, 6 months after surgery and at the last follow-up were (49.5±5.9)%, (28.5±4.6)% and (19.2±4.8)% respectively, significantly lower than (78.8±6.8)% before surgery ( P<0.01), and a statistically singnificant decrease was found over follow-up time ( P<0.01). The VBI values at 1 day, 6 months after surgery and at the last follow-up were (76.6±4.5)%, (76.3±4.0)% and (76.1±3.8)% respectively, significantly higher than (58.9±5.8)% before surgery ( P<0.01), while there were no significant differences among those at 1 day, 6 months after surgery and at the last follow-up ( P>0.05). The KA values at 1 day, 6 months after surgery and at the last follow-up were (12.4±2.7)°, (12.6±2.5)° and (12.8±2.9)° respectively, significantly lower than (20.8±3.6)° before surgery ( P<0.01), while there were no significant differences among those at 1 day, 6 months after surgery and at the last follow-up ( P>0.05). According to the Odom criteria, 20 patients were rated excellent and 5 good at the last follow-up, with an excellent and good rate of 100%. Intraoperative asymptomatic bone cement leakage occurred in 3 patients (12%), including 2 with intervertebral leakage and 1 with lateral vertebral leakage. No adjacent vertebral body or other vertebral fracture was observed during the follow-up. Conclusions:For patients with refracture of injured vertebrae after vertebral augmentation for OVCF, the secondary targeted PVP has advantages of attenuation of the lower back pain, improvement of the quality of life, restoration of the height of refractured vertebrae, correction of the local kyphosis, and a low incidence of complications.

Objective:To evaluate the guiding value of ultrasound-guided selective nerve root block in the surgical treatment of multilevel lumbar degeneration.Methods:Retrospective case-control study was used. Clinical data of 47 patients with multi-level lumbar degeneration who underwent decompression surgery in Honghui Hospital, Xi′an Jiaotong University from January 2019 to December 2021 were retrospectively analyzed. They were divided into nerve root block group ( n=22)and non-nerve root block group( n=25) according to whether ultrasound-guided selective nerve root block was performed before decompression surgery. The operation time, intraoperative blood loss, number of decompression laminae, postoperative drainage volume and length of stay of the two groups were recorded and compared. The visual analogue scale of low back pain, the visual analogue scale (VAS) of leg pain, the Japanese orthopaedic association (JOA) score and Oswestry disability index (ODI) score were all compared before surgery and during follow-up between the two groups. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the paired t-test. Chi-square test was used for counting data. Results:All 47 patients successfully completed the operation without any serious complications such as neurovascular injury. All patients were followed up for (27.6±7.5)months. In the nerve root block group, the operation time, intraoperative blood loss, number of decompression laminae, postoperative drainage volume and hospital stay were (90.5±12.6) min, (110.5±15.8) mL, 1.2±0.8, (85.6±15.8) mL, (6.2±2.8) d, respectively. In the non-root block group, they were (190.6±25.5) min, (450.5±24.8) mL, 3.8±1.6, (210.5±16.8) mL, (9.5±2.2) d, respectively. The above indexes in the nerve root closure group were less than those in the non-root closure group, and the difference was significant between the two groups ( P< 0.05). The scores of VAS of low back pain and leg pain, JOA and ODI in both groups were significantly improved after surgery and during the follow-up period when compared with those of pre-operation ( P< 0.05). The VAS scores of low back pain on the 3rd day, 6 months after operation and at the last follow-up in the nerve block group were 3.2±1.4, 1.4±0.8, 0.5±0.2, the JOA scores were 15.8±4.3, 21.3±5.6, 25.6±1.4, and the ODI scores were 50.6±10.3, 22.8±7.8, 16.8±4.2, respectively. The VAS scores of low back pain on the 3rd day, 6 months after operation and at the last follow-up in the non-nerve block group were 5.1±1.8, 3.4±1.2, 1.8±0.5, the JOA scores were 14.1±4.8, 20.5±3.2, 24.2±1.8, and the ODI scores were 60.5±9.8, 31.6±8.2 and 21.3±5.5, respectively. The difference between the two groups was statistically significant ( P<0.05). However, there was no statistical difference in the VAS scores of leg pain between the two groups after surgery and during follow-up ( P>0.05). At the last follow-up, the internal fixation position of the two groups was good, no loosening and displacement, and bone graft fusion was good. Conclusion:For patients with multi-level lumbar degeneration, ultrasound-guided selective nerve root block before surgery can identify the responsible segment, and selective decompression and fusion based on this can effectively reduce surgical trauma, while improving patients′ back and leg pain and physical function, which has important surgical guidance value.

Objective:To explore the efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy in stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) patients in the real world.Methods:The clinical data of 139 patients with stage Ⅲ-ⅣA ESCC who underwent radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. Patients were divided into a control group ( n=85) and a consolidation chemotherapy group ( n=54) based on whether they underwent consolidation chemotherapy after radical radiotherapy and chemotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) between the two groups were compared. The Kaplan-Meier method was used to draw survival curves and log-rank tests were conducted. The Cox proportional risk model was used for univariate and multivariate analysis. Results:The ORR of the control group and the consolidation chemotherapy group were 44.71% (38/85) and 66.67% (36/54), respectively, with a statistically significant difference ( χ2=5.54, P=0.018) ; the DCR were 70.59% (60/85) and 87.04% (47/54), respectively, with a statistically significant difference ( χ2=5.04, P=0.025). The median PFS of the two groups of patients were 9.0 and 13.1 months, respectively, with a statistically significant difference ( χ2=12.74, P<0.001) ; the median OS were 15.0 and 20.6 months, respectively, with a statistically significant difference ( χ2=24.75, P<0.001). The median OS of ESCC patients in two subgroups of cT 3-4N 1-3M 0 were 16.0 and 30.8 months, respectively, with a statistically significant difference ( χ2=23.49, P<0.001). Univariate analysis showed that tumor length ( HR=1.57, 95% CI: 1.04-2.36, P=0.032), objective response ( HR=0.08, 95% CI: 0.04-0.17, P<0.001), and consolidation chemotherapy ( HR=0.32, 95% CI: 0.20-0.51, P<0.001) were all influencing factors for OS in ESCC patients undergoing radical radiotherapy and chemotherapy in stages Ⅲ-ⅣA. Multivariate analysis showed that tumor length ( HR=1.59, 95% CI: 1.05-2.43, P=0.030), objective response ( HR=0.05, 95% CI: 0.02-0.10, P<0.001), and consolidation chemotherapy ( HR=0.22, 95% CI: 0.13-0.36, P<0.001) were all independent influencing factors for OS in stage Ⅲ-ⅣA ESCC patients undergoing radiotherapy and chemotherapy. In terms of safety, the consolidation chemotherapy group experienced 7 adverse reactions mainly gastrointestinal reaction and leukopenia, including 5 cases of grade 1-2 and 2 cases of grade 3-4; 22 cases of adverse reactions occurred in the control group including 16 cases of grade 1-2 and 6 cases of grade 3-4 mainly including neutropenia, thrombocytopenia, anemia and digestive tract reaction. The incidence rates of adverse reactions in the two groups were 12.96% (7/54) and 25.88% (22/85), respectively, with no statistically significant difference ( χ2=3.34, P=0.068) . Conclusion:After radical radiotherapy and chemotherapy, consolidation chemotherapy can significantly improve the prognosis of stage Ⅲ-ⅣA ESCC patients, and the overall adverse reactions are controllable.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.